Cancer is considered to be a serious and pervasive disease. The National Cancer Institute has estimated that in the United States alone, 1 in 3 people will be struck with cancer during their lifetime. Moreover approximately 50% to 60% of people contracting cancer will eventually succumb to the disease. One particularly prevalent form of cancer, especially among women, is breast cancer. The incidence of breast cancer, a leading cause of death in women, has been gradually increasing in the United States over the last thirty years. In 1997, it was estimated that 181,000 new cases were reported in the U.S., and that 44,000 people would die of breast cancer (Parker et al, 1997, CA Cancer J. Clin. 47:5-27; Chu et al, 1996, J. Nat. Cancer Inst. 88:1571-1579). While the pathogenesis of breast cancer is unclear, transformation of normal breast epithelium to a malignant phenotype may be the result of genetic factors, especially in women under 30 (Miki et al., 1994, Science, 266:66-71). The discovery and characterization of BRCA1 and BRCA2 has expanded our knowledge of genetic factors that can contribute to familial breast cancer. Germ-line mutations within these two loci are associated with a 50 to 85% lifetime risk of breast and/or ovarian cancer (Casey, 1997, Curr. Opin. Oncol. 9:88-93; Marcus et al., 1996, Cancer 77:697-709). However, it is likely that other genetic and non-genetic factors also have a significant effect on the etiology of the disease.
Several general strategies have been developed to destroy cancer within the body. One method utilizes cytotoxic chemotherapeutics. These compounds are administered to cancer patients to preferentially destroy rapidly dividing malignant cells over normal, healthy cells. Examples of such compounds include 5-fluorouracil, cisplatin, and methotrexate. However, destruction of normal healthy cells by chemotherapeutics often leaves patients weakened and ill. Another approach involves reducing the supply of oxygen and nutrients to a tumor to prevent its growth by blocking the formation of new blood vessels, a process know as angiogenesis. Angiogenesis involves the formation of new blood vessels from existing blood vessels in response to various cell signals. Additional approaches include cancer vaccines and treatment of patients with antibodies directed to antigens that are overexpressed in cancer cells, such as the her2 receptor in breast cancer cells.
Another approach to treat cancer is to block the process of metastasis. Many tumors, such as breast tumors, can be either benign or malignant. Benign tumors are localized to one part of the body and do not spread to other parts of the body, and are not a threat to life. They can usually be removed, and in most cases, do not recur in patients. Malignant tumors, however, are cancerous and can invade and damage nearby tissues and organs, such as by entering the bloodstream or the lymphatic system, in a process known as metastasis. Thus, a benign breast tumor can metastasize into the liver or the lungs, resulting in death. Accordingly, anti-metastatic agents hold great promise in cancer treatment and in reducing mortality. In addition, such agents can also be used prophylactically after the removal of a precancerous tumor.
It would be advantageous to have new compositions and methods available for inhibiting tumor metastasis. It would also be advantageous to have new methods for identifying such compositions and methods. The present invention provides such compositions and methods.